Qualitative and Quantitative Features of Music Reported to Support Peak Mystical Experiences during Psychedelic Therapy Sessions

Psilocybin is a classic (serotonergic) hallucinogen (“psychedelic” drug) that may occasion mystical experiences (characterized by a profound feeling of oneness or unity) during acute effects. Such experiences may have therapeutic value. Research and clinical applications of psychedelics usually include music listening during acute drug effects, based on the expectation that music will provide psychological support during the acute effects of psychedelic drugs, and may even facilitate the occurrence of mystical experiences. However, the features of music chosen to support the different phases of drug effects are not well-specified. As a result, there is currently neither real guidance for the selection of music nor standardization of the music used to support clinical trials with psychedelic drugs across various research groups or therapists. A description of the features of music found to be supportive of mystical experience will allow for the standardization and optimization of the delivery of psychedelic drugs in both research trials and therapeutic contexts. To this end, we conducted an anonymous survey of individuals with extensive experience administering psilocybin or psilocybin-containing mushrooms under research or therapeutic conditions, in order to identify the features of commonly used musical selections that have been found by therapists and research staff to be supportive of mystical experiences within a psilocybin session. Ten respondents yielded 24 unique recommendations of musical stimuli supportive of peak effects with psilocybin, and 24 unique recommendations of musical stimuli supportive of the period leading up to a peak experience. Qualitative analysis (expert rating of musical and music-theoretic features of the recommended stimuli) and quantitative analysis (using signal processing and music-information retrieval methods) of 22 of these stimuli yielded a description of peak period music that was characterized by regular, predictable, formulaic phrase structure and orchestration, a feeling of continuous movement and forward motion that slowly builds over time, and lower perceptual brightness when compared to pre peak music. These results provide a description of music that may be optimally supportive of peak psychedelic experiences. This description can be used to guide the selection and composition of music for future psychedelic research and therapy sessions

Dose-related Effects of Salvinorin A in Humans: Dissociative, Hallucinogenic, and Memory Effects

RATIONALE: Salvinorin A is a kappa opioid agonist and the principal psychoactive constituent of the plant Salvia divinorum, which has increased in popularity as a recreational drug over the past decade. Few human studies have examined salvinorin A. OBJECTIVE: This double-blind, placebo-controlled study evaluated the dose-related effects of inhaled salvinorin A in individuals with histories of hallucinogen use. METHODS: Eight healthy hallucinogen-using adults inhaled up to 16 doses of salvinorin A (0.375 - 21 μg/kg) in ascending order. Physiological, behavioral, and subjective effects were assessed every 2 min for 60 min after administration. Qualitative subjective effects were assessed retrospectively via questionnaires at the end of sessions. Persisting effects were assessed 1 month later. RESULTS: Orderly dose-related effects peaked at 2 min and then rapidly dissipated, replicating previous findings. Subjective effects were intense, with maximal drug strength ratings or unresponsiveness frequently observed at high doses. Questionnaires assessing qualitative effects (Hallucinogen Rating Scale, Pharmacological Class Questionnaire) suggested some overlap with serotonergically mediated classic hallucinogens. Salvinorin A also produced dose-related dissociative effects and impairments in recall/recognition memory. At 1-month follow-up, there was no evidence of persisting adverse effects. Participants reported salvinorin A effects were qualitatively different from other drugs. CONCLUSIONS: Salvinorin A produces a unique profile of subjective and cognitive effects, including strong dissociative effects and memory impairment, which only partially overlap with classic hallucinogen effects. Along with nonhuman studies of salvinorin A, these results are important for understanding the neurobiology of the kappa opioid system and may ultimately have important therapeutic applications

Human psychopharmacology and dose-effects of salvinorin A, a kappa-opioid agonist hallucinogen present in the plant Salvia divinorum

Salvinorin A is a potent, selective nonnitrogenous kappa opioid agonist and the known psychoactive constituent of Salvia divinorum, a member of the mint family that has been used for centuries by Mazatec shamans of Mexico for divination and spiritual healing. Salvia divinorum has over the last several years gained increased popularity as a recreational drug. This is a double-blind, placebo controlled study of salvinorin A in 4 psychologically and physically healthy hallucinogen-using adults. Across sessions, participants inhaled 16 ascending doses of salvinorin A and 4 intermixed placebo doses under comfortable and supportive conditions. Doses ranged from 0.375 μg/kg to 21 μg/kg. Subject-rated drug strength was assessed every 2 minutes for 60 minutes after inhalation. Orderly time- and dose-related effects were observed. Drug strength ratings peaked at 2 minutes (first time point) and definite subjective effects were no longer present at approximately 20 minutes after inhalation. Dose-related increases were observed on questionnaire measures of mystical-type experience (Mysticism Scale) and subjective effects associated with classic serotonergic (5-HT2A) hallucinogens (Hallucinogen Rating Scale). Salvinorin A did not significantly increase heart rate or blood pressure. Participant narratives indicated intense experiences characterized by disruptions in vestibular and interoceptive signals (e.g., change in spatial orientation, pressure on the body) and unusual and sometimes recurring themes across sessions such as revisiting childhood memories, cartoon-like imagery, and contact with entities. Under these prepared and supportive conditions, salvinorin A occasioned a unique profile of subjective effects having similarities to classic hallucinogens, including mystical-type effects

Oral vitamin C and endothelial function in smokers: short-term improvement, but no sustained beneficial effect

AbstractOBJECTIVESTo test the hypothesis that antioxidant therapy would improve endothelial function in smokers.BACKGROUNDSeveral studies have documented a beneficial effect of short-term oral or parenteral vitamin C on endothelial physiology in subjects with early arterial dysfunction. Possible long-term effects of vitamin C on endothelial function, however, are not known.METHODSWe studied the effects of short- and long-term oral vitamin C therapy on endothelial function in 20 healthy young adult smokers (age 36 ± 6 years, 8 male subjects, 21 ± 10 pack-years). Each subject was studied at baseline, 2 h after a single dose of 2 g vitamin C and 8 weeks after taking 1 g vitamin C daily, and after placebo, in a randomized double-blind crossover study. Blood samples were analyzed for plasma ascorbate levels and endothelial function was measured as flow-mediated dilation of the brachial artery, using high resolution ultrasound. Nitroglycerin-mediated dilation (endothelium-independent) was also measured at each visit.RESULTSAt baseline, plasma ascorbate level was low in the smokers (42 ± 21 μmol/liter; normal range, 50 to 150 μmol/liter), increased with vitamin C therapy after 2 h to 120 ± 54 μmol/liter (p < 0.001) and remained elevated after eight weeks of supplementation at 92 ± 32 μmol/liter (p < 0.001, compared with placebo). Flow-mediated dilation, however, increased at 2 h (from 2.8 ± 2.0% to 6.3 ± 2.8%, p < 0.001), but there was no sustained beneficial effect after eight weeks (3.9 ± 3.2%, p = 0.26). Nitroglycerin-mediated dilation was unchanged throughout.CONCLUSIONOral vitamin C therapy improves endothelial dysfunction in the short term in healthy young smokers, but it has no beneficial long-term effect, despite sustained elevation of plasma ascorbate levels

Geodesics in spacetimes with expanding impulsive gravitational waves

We study geodesic motion in expanding spherical impulsive gravitational waves propagating in a Minkowski background. Employing the continuous form of the metric we find and examine a large family of geometrically preferred geodesics. For the special class of axially symmetric spacetimes with the spherical impulse generated by a snapping cosmic string we give a detailed physical interpretation of the motion of test particles.Comment: 12 pages, Revtex, final versio

Decoherence and wave function collapse

The possibility of consistency between the basic quantum principles of quantum mechanics and wave function collapse is reexamined. A specific interpretation of environment is proposed for this aim and applied to decoherence. When the organization of a measuring apparatus is taken into account, this approach leads also to an interpretation of wave function collapse, which would result in principle from the same interactions with environment as decoherence. This proposal is shown consistent with the non-separable character of quantum mechanics

The Acute Effects of the Atypical Dissociative Hallucinogen Salvinorin A on Functional Connectivity in the Human Brain

Salvinorin A (SA) is a κ-opioid receptor agonist and atypical dissociative hallucinogen found in Salvia divinorum. Despite the resurgence of hallucinogen studies, the effects of κ-opioid agonists on human brain function are not well-understood. This placebo-controlled, within-subject study used functional magnetic resonance imaging for the first time to explore the effects of inhaled SA on strength, variability, and entropy of functional connectivity (static, dynamic, and entropic functional connectivity, respectively, or sFC, dFC, and eFC). SA tended to decrease within-network sFC but increase between-network sFC, with the most prominent effect being attenuation of the default mode network (DMN) during the first half of a 20-min scan (i.e., during peak effects). SA reduced brainwide dFC but increased brainwide eFC, though only the former effect survived multiple comparison corrections. Finally, using connectome-based classification, most models trained on dFC network interactions could accurately classify the first half of SA scans. In contrast, few models trained on within- or between-network sFC and eFC performed above chance. Notably, models trained on within-DMN sFC and eFC performed better than models trained on other network interactions. This pattern of SA effects on human brain function is strikingly similar to that of other hallucinogens, necessitating studies of direct comparisons

LC-MS/MS quantification of salvinorin A from biological fluids

A facile method for quantifying the concentration of the powerful and widely available hallucinogen salvinorin A (a selective kappa opioid agonist) from non-human primate cerebrospinal fluid (CSF) and human plasma has been developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in positive electrospray ionization (ESI) mode. With CSF solid phase extraction can be avoided completely by simply diluting each sample to 10 % (v/v) acetonitrile, 1 % (v/v) formic acid and injecting under high aqueous conditions for analyte focusing. Extensive plasma sample preparation was investigated including protein precipitation, SPE column selection, and plasma particulate removal. Human plasma samples were centrifuged at 21,000 × gravity for 4 minutes to obtain clear particulate-free plasma, from which 300 μl was spiked with internal standard and loaded onto a C18 SPE column with a 100 mg mL−1 loading capacity. Guard columns (C18, hand packed 1 mm × 20 mm) were exchanged after backpressure increased above 4600psi, about 250 injections. A shallow acetonitrile/water gradient was used, 29 to 33% CH3CN over 8 minutes to elute salvinorin A. Reduction of chemical noise was achieved using tandem mass spectrometry with multiple reaction monitoring while sensitivity increases were observed using a 50 μL injection volume onto a small bore analytical column (C18, 1 mm ID × 50 mm) thus increasing peak concentration. Limits of quantification were found to be 0.0125 ng mL−1 (CSF) and 0.05 ng mL−1 (plasma) with interday precision and accuracy below 1.7 % and 9.42 % (CSF) and 3.47 % and 12.37 % (plasma) respectively. This method was used to determine the concentration of salvinorin A from an in vivo Rhesus monkey study and a trial of healthy human research participants, using behaviorally active doses

Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study

5-MeO-DMT is a psychoactive substance found in high concentrations in the bufotoxin of the Colorado River Toad (Bufo alvarius). Emerging evidence suggests that vaporized 5-MeO-DMT may occasion mystical experiences of comparable intensity to those occasioned by more widely studied psychedelics such as psilocybin, but no empirical study has tested this hypothesis. Data was obtained from 20 individuals (Mage = 38.9, ± 10.7; male = 55%, Caucasian = 85%) who were administered 5-MeO-DMT as part of a psychospiritual retreat program in Mexico. All participants received 50 mg of inhaled vaporized toad bufotoxin which contains 5-MeO-DMT and completed the Mystical Experience Questionnaire (MEQ30) approximately 4–6 h after their session. Administration of 5-MeO-DMT occasioned strong mystical experiences (MEQ30 Overall Mintensity = 4.17, ± 0.64, range 0–5) and the majority (n = 15, 75%) had “a complete mystical experience” (≥60% on all MEQ30 subscales). Compared to a prior laboratory-based psilocybin study, there were no differences in the intensity of mystical effects between 5-MeO-DMT and a high dose (30 mg/70 kg) of psilocybin, but the intensity of mystical effects was significantly higher in the 5-MeO-DMT sample compared to moderate/high dose (20 mg/70 kg) of psilocybin (MEQ30 Total Score: p = 0.02, d = 0.81). Administration of vaporized 5-MeO-DMT reliably occasioned complete mystical experiences in 75% of individuals and was similar in intensity to high dose psilocybin administered in a laboratory setting. The short duration of action may be advantageous for clinical interventions and for studying mystical-type experiences